Vascular Organoids to Model Inherited Vascular Diseases

Hereditary Hemorrhagic Telangiectasia (HHT) is a debilitating condition characterized by vascular malformations and pulmonary hypertension (PH). Mutations in the ALK1 gene are a major cause of HHT-associated PH, but the underlying cellular and molecular mechanisms are poorly understood. To address this knowledge gap, this proposal aims to generate biomimetic vascular organoids from induced pluripotent stem cells (iPSCs) harboring two common ALK1 mutations. These organoids could provide a more realistic and physiologically relevant platform for studying the process of vascular remodeling (VAR) in HHT associated PH. This information could lead to the development of new therapeutic strategies for this devastating disease.